Meiosis is the specialized cell cycle that leads to the production of gametes (eggs or sperm) that carry a single copy of each chromosome. The most common cause of birth defects in humans is aneuploidy, which occurs when an error during meiosis results in gametes with the wrong number of chromosomes. Aneuploidy is usually lethal, while any survivors have severe medical conditions such as Down syndrome, where affected individuals have three copies of chromosome 21. Over 90% of human aneuploidies arise during the process of egg production, which makes the study of female meiosis a critical issue for human health. One step found in the cell cycles of nearly all species is congression, where the cell lines up its chromosomes in preparation for division. For example, the chemical Bisphenol A (BPA, a known endocrine disruptor) recently was shown to cause congression errors during female meiosis in mice, and those higher rates of congression errors are correlated with higher rates of aneuploidy. On the basis of this research, BPA is being phased out from consumer plastics. Therefore, increasing our understanding of the process of congression is a key component of the study of female meiosis and has applications to public health policy. This proposal will use the fruit fly Drosophila melanogaster as a model system to study congression during female meiosis. The first goal of this project is to conduct a candidate survey of carefully selected mutant genotypes, to see if those mutants cause disruptions in congression. These mutants will be assayed for egg maturation rate, chromosome orientation during congression, and spindle defects. If successful, this will begin genetically dissecting the chromosome congression pathway. The second goal of this project is to test the hypothesis that aneuploidy in certain mutants is caused by congression defects. This will be accomplished by analyzing a series of mps1 mutants, which can still complete congression but undergo widely varying rates of aneuploidy. The rates of aneuploidy will be measured and compared to the rate of congression defects. If the hypothesis is correct, these two rates should be highly correlated with each other. Finally, the project will revisit the process of heterologous segregation, where two aberrant chromosomes that lack normal pairing partners are capable of segregating away from each other. This process was first identified over 70 years ago, but no satisfactory mechanism to co-segregate chromosomes that cannot pair has ever been documented. This project will test the hypothesis that the need to congress the chromosomes into a small volume can explain how the chromosomes co-segregate without pairing. This will be tested by genetically measuring the rate of heterologous segregation, and cytologically measuring the rate of coorientation during congression, of a series of genotypes known to undergo this process. If the hypothesis is correct, these two rates should be equal. If successful, this will solve one of the longest-standing puzzles in the field of Drosophila female meiosis. PUBLIC HEALTH RELEVANCE: This project will use the fruit fly (Drosophila melanogaster) as a model system to study chromosome congression during egg development. Congression is the process where the chromosomes all become lined up before the cell divides. This is important for public health because errors that occur during egg development are the single most common source of birth defects, and can cause diseases such as Down syndrome.